Reactivity effects acid-base equilibria

On the other hand, an increase in acidity should shift the acid-base equilibrium of the aniline (Scheme 3-11) further to the side of the anilinium ion, which is much less reactive. The effects of the two equilibria in Schemes 3-8 and 3-11 should therefore be approximately equal and opposite, so that from these arguments alone one would not expect the rate increase observed for region B. 

Sn2 reactions with anionic nucleophiles fall into this class, and observations are generally in accord with the qualitative prediction. Unusual effects may be seen in solvents of low dielectric constant where ion pairing is extensive, and we have already commented on the enhanced nucleophilic reactivity of anionic nucleophiles in dipolar aprotic solvents owing to their relative desolvation in these solvents. Another important class of ion-molecule reaction is the hydroxide-catalyzed hydrolysis of neutral esters and amides. Because these reactions are carried out in hydroxy lie solvents, the general medium effect is confounded with the acid-base equilibria of the mixed solvent lyate species. (This same problem occurs with Sn2 reactions in hydroxylic solvents.) This equilibrium is established in alcohol-water mixtures ... 

In this solvent the reaction is catalyzed by small amounts of trimethyl-amine and especially pyridine (cf. 9). The same effect occurs in the reaction of iV -methylaniline with 2-iV -methylanilino-4,6-dichloro-s-triazine. In benzene solution, the amine hydrochloride is so insoluble that the reaction could be followed by recovery. of the salt. However, this precluded study mider Bitter and Zollinger s conditions of catalysis by strong mineral acids in the sense of Banks (acid-base pre-equilibrium in solution). Instead, a new catalytic effect was revealed when the influence of organic acids was tested. This was assumed to depend on the bifunctional character of these catalysts, which act as both a proton donor and an acceptor in the transition state. In striking agreement with this conclusion, a-pyridone is very reactive and o-nitrophenol is not. Furthermore, since neither y-pyridone nor -nitrophenol are active, the structure of the catalyst must meet the conformational requirements for a cyclic transition state. Probably a concerted process involving structure 10 in the rate-determining step... 

Scatter in free energy correlations may also be caused by a statistical effect when more than one reaction centre can be involved.The reactivity of a base or nucleophile possessing q identical basic or nucleophilic sites compared with a dissociation equilibrium where the conjugate acid possesses p identical acidic sites requires the following statistical correction to the simple Bronsted type relationship (Equations 23 and 24). 

Notably, the inhibiting effect of NH3 on the Fast SCR activity at low temperature is not due to the ammonia competitive chemisorption on the catalytic sites, but occurs because ammonia captures a key intermediate in an unreactive form. In this respect, one way to partially prevent this undesired effect is to modify the equilibrium of ammonium nitrate dissociation, e.g., by increasing the temperature or by decreasing the gas-phase ammonia concentration. Since the blocking effect is related to the acid properties of the formed nitrates, another possibility to moderate its negative impact on the Fast SCR reactivity at low T would be to modify the catalyst acid/base properties in order to favor the interaction of ammonia with the catalyst sites rather than with the nitrates [5]. 

There are some difficulties with testing this experimentally. The first is that it is not easy to match the same set of bases to electrophiles of quite different reactivity. A second is that the most readily available equilibrium constants characterizing the nucleophiles are pAias of the conjugate acids, which do not necessarily correlate reactivities toward carbocations. Thirdly, one should avoid reactions influenced by diffusion control. Finally, care has to be taken with steric and solvent effects. 

Quantitative structure-activity relationship studies are of great importance in modern chemistry. From their origin in the study of organic chemistry dating back to the 19th century, these studies have relied on some empirical and qualitative rules about the reactivity similarities of compounds with similar structures. The most significant development in QSARs occurred with the work of Louis Hammett (1894-1987), who correlated some electronic properties of organic acids and bases with their equilibrium constants and reactivity (Johnson, 1973). Hammett postulated that the effect... 

Consider the case of an acyl chloride. The chlorine is an inductive electron with-drawer and a resonance electron donor. As we saw in Chapter 17, the inductive effect is stronger. (Recall that chlorine is not a very strong resonance electron donor because the long C—Cl bond and the size difference between the 3p AO on the Cl and the 2p AO on the C result in poor overlap of these orbitals.) In addition, chloride anion is a very weak base. Overall, acyl chlorides are the most reactive of the carboxylic acid derivatives discussed here and are the least favored at equilibrium. 

Until relatively recently no kinetic studies on the nitrosation of alcohols had been reported, presumably since the reactions are very rapid and require special techniques. Some kinetic measurements on the reverse reaction, the hydrolysis of alkyl nitrites have been reported here conventional kinetic methods were used. Early workers examined the reactions of the series methyl, ethyl, i-propyl and t-butyl nitrites in an acetic acid-acetate buffer and found a small increase in rate constant along the series (Skrabal et a ., 1939). Later Allen measured the rate constants for the hydrolysis of a number of alkyl nitrites in aqueous dioxan solvent for both acid- and base-catalysed reactions (Allen, 1954). The rate constants for the O-nitrosation of alcohols were determined indirectly by measurement of the overall equilibrium constant for the process, by noting the change in the rate constant for the nitrosation of phenol in the presence of added alcohols. These, combined with the known data for the reverse hydrolysis reaction, enabled the rate constants for the forward reaction to be obtained (Schmid and Riedl, 1967). The reactivity sequence MeOH > EtOH > i-PrOH > t-BuOH was deduced, and attributed to a steric effect. 

The relative strengths of weakly basic solvents are evaluated from the extent of protonation of hexamethylbenzene by trifluoro-methanesulfonic acid (TFMSA) in those solvents or from the effect of added base on the same protonation in solution in trifluoroacetic acid (TFA), the weakest base investigated. The basicity TFA < di-fluoroacetic acid < dichloroacetic acid (DCA) < chloroacetic acid < acetic acid parallels the nucleophilicity. 2-Nitropropane appears to be a significantly stronger base than DC A by the first approach, although in the second type of measurement, the two have essentially equal basicity. The discrepancy is due to an interaction, possible for hydroxylic solvents such as DC A, with the anion of TFMSA. This anion stabilization is a determining factor of carbocationic reactivity in chemical reactions, including solvolysis. A distinction is made between carbocation stability, determined by structure, and persistence (existence at equilibrium, e.g., in superacids), determined by environment, that is, by anion stabilization. 

Comparison of relative reactivities at constant steric effects in terms of a few selected Hammett s p values is shown in Table VII for ArS- and in Table VIII for anilines. Although some of the data in Table VII are based only on two points, clearly the p values are structure-dependent. Moreover, these values show no clear trend. The reactivity of P,P-dihalovinyl sulfones are similar to those of the P-halovinyl sulfones, but their p values are much lower. The addition reactions with ArS- show higher p values than for most of the substitutions, but for the structurally similar vinyl sulfones, the p for the substitution is higher. In general, the p values for the anilines are significantly higher, but this fact does not necessarily mean an earlier transition state for the anionic nucleophiles because the p values for the equilibrium acidities of the anilinium ions are higher than those for the thiols. 

Aromatic esters It is possible to alkylate benzoic acids directly, without the need to prepare reactive potassium salts in a separate step, because they can be generated in situ by reacting the acid with a base (potassium carbonate or hydroxide) in the presence of a phase-transfer catalyst. As an illustration of this principle, a volatile polar molecule is a by-product, eliminated as a result of exposure to MW (Eq. 4), and the equilibrium is shifted to completion. The second effect of irradiation is activation of the alkylation step itself (Eq. 5). All the reagents can be used in the theoretical stoichiometry. Some indicative results are given in Table 6.4 [9]. 

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